Histomonas meleagridis is a protozoan obligate parasite of poultry causing the severe disease histomoniasis, also known as enterohepatitis or blackhead. The epidemiology of the disease in a population varies from mild and slumbering to severe and acute outbreaks. Histomoniasis is characterised by depressed animals, loss of weight, yellow fluid droppings and severe necrotic lesions in caeca and liver causing pain, suffering and death. Turkeys are most sensitive to the disease with reports of 100% mortality within one flock but also broiler chickens and laying hens show mortality up to 20% accompanied by high morbidity and decreased Zootechnical parameters. Also other poultry species are susceptible for histomoniasis.
In nature infection of birds occurs normally by infestation of the intermediate host Heterakis gallinarum. H. gallinarum is a caecal parasitic nematode of poultry. H. meleagridis nestle in the nematode eggs to obtain protection against environmental impact. H. meleagridis is very fragile and can only survive for a very short period in the outer world but protected in the nematode egg the parasite can stay infectious for long time. When the infected worm or worm eggs are taken up the H. meleagridis remains protected against crop and stomach activity and is released in the caeca of the host by excretion or digesting of the worm or larvae. After a reproduction period in the lumen of the caeca the parasite penetrates the gut wall and travels through the bloodstream to the liver.
Domestic fowl however can be infected without the presence of H. gallinarum. In poultry houses temperature and climate conditions allows H. meleagridis to survive a few hours in the environment. Because of the high bird density the chance for the parasite to be picked by a next host is realistic. The transmission of the parasite is by direct contact of the cloaca with contaminated faeces of infected birds (1: McDougald & Fuller, 2005).
The aminoglycosides, also aminocyclitols, are a group of bactericidal antibiotics derived from the genus Streptomyces or Micromonospora (gentamicin and sisomicin). They are polycationic compounds with cyclic amino-sugars attached by glycosidic linkages. They all have a similar antimicrobial spectrum, broadly similar toxicological features and pharmacokinetics (J. F. Prescott & J. Desmond Baggot: Antimicrobial Therapy in Veterinary Medicine. Blackwell Scientific Publications, The Merck Index, Fourteenth Edition, Martindale, The ExtraPharmacopoeia. The Pharmaceutical Press and N. H. Booth & L. E. McDonald, Veterinary Pharmacology and Therapeutics. Iowa State University Press/AMES).
Apramycin (C21H41N5011) (cas-37321-09-8) is an aminoglycoside antibiotic sold e.g. under the trade name Apralan® (ELANCO U.K.) produced by microorganisms of the Streptomyces sp. Genus (Streptomyces tenebraius) (Ryden R & Moore B. J. J. Antimicrob Chemother. Vol. 3 p 609 (1977)). It is structurally related to kanamycin and gentamicin and has a broad spectrum of bacterial activity.
Previous research has been conducted with limited success to use of apramycin as a chemotherapeutic agent for treatment of histomoniasis in chickens. Its use in-vivo was rendered ineffective when applied at 300 ppm in broilers. Only some reduction of liver lesions but no amelioration of caecal histomoniasis lesions or weight gain could be achieved (2: Hu & McDougald, 2002).
No significant treatment effect was seen for turkeys (3: McDougald, 2003).